Vagus nerve stimulation for pediatric patients with intractable epilepsy between 3 and 6 years of age: study protocol for a double-blind, randomized control trial - PubMed

doi: 10.1186/s13063-018-3087-4.

Zhao Yang  ³ , Qingzhu Liu  ² , Jianxiang Liao  ⁴ , Fei Yin  ^{5   6} , Yanhui Chen  ^{7   8} , Liping Zou  ⁹ , Baomin Li  ¹⁰ , Yuxing Gao  ¹¹ , Xiaomei Shu  ¹² , Shaoping Huang  ¹³ , Feng Gao  ¹⁴ , Jianmin Liang  ^{15   16} , Su Fang Lin  ⁴ , Jing Peng  ^{5   6} , Shiwei Song  ^{8   17} , Jing Wang  ⁹ , Chao Che  ¹⁰ , Wenxiu Sun  ¹¹ , Maoqiang Tian  ¹² , Lin Yang  ¹³ , Yi Hua  ¹⁴ , Yunpeng Hao  ¹⁵ , Lixin Cai  ¹⁸ , Luming Li  ^{19   20   21   22} , Yuwu Jiang  ^{23   24}

Background: Recent clinical observations have reported the potential benefit of vagus nerve stimulation (VNS) as an adjunctive therapy for pediatric epilepsy. Preliminary evidence suggests that VNS treatment is effective for seizure reduction and mental development in young participants between 3 and 6 years of age who suffer from intractable epilepsy. However, robust clinical evidence for quantifying the difference of the efficacy and safety of VNS treatment in this specific patient population has yet to be reported.

Methods/design: A two-armed, multicenter, randomized, double-blind, prospective trial will be carried out to evaluate whether VNS is beneficial and safe for pediatric epilepsy. Pediatric participants aged between 3 to 6 years old with intractable epilepsy will be recruited and randomly assigned to experimental and control groups with a 1:1 allocation using a computer-generating randomization schedule. Before enrollment, informed consent will be signed by the parents of the participants and the study researchers. Participants in the experimental group will receive electrical stimulation over 24 weeks under standard stimulation parameters. Participants in the control group will not receive any stimulation during the 12 weeks of the double-blind period. The guardians of the participants are required to keep a detailed diary to record seizure activity. Outcome assessments including seizure frequency, Gesell Mental Developmental Scale scores, use of antiepileptic drugs and dosages, and adverse events will be collected at baseline, 6, 12, 18 and/or 24 weeks after electrical stimulation is initiated. The effects of treatment will be analyzed with time and treatment group comparisons.

Discussion: This trial will evaluate quantitative differences in efficacy and safety with/without VNS treatment for pediatric participants aged between 3 to 6 years with intractable epilepsy and will explore whether the current age range of VNS therapy can be expanded.

Trial registration: ClinicalTrials.gov, ID: NCT03062514 , Registered on 23 February 2017.

Ethics approval and consent to participate

The VNS-PIE study received ethical approval from the Clinical Trial Ethics Committee of Peking University First Hospital, covering all participating sites. Important changes to the protocol will be submitted to the Ethics Committee for review. Informed consent will be obtained from all participants in the trial.

Consent for publication

Consent forms for the trial include consent for publication of results in peer-reviewed journals.

Competing interests

Salary and grant supports in this trial are supported by the sponsor. No additional reporting is allowed until the final report of the trial is completed, with the exception of consent by the sponsor. Information on the sponsor’s and investigator’s publishing policies will be described in their clinical trial contract.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

1. 1. Moshé SL, et al. Epilepsy: new advances. Lancet. 2015;385(9971):884–898. - PubMed
2. 1. Guerrini R. Epilepsy in children. Lancet. 2006;367(9509):499–524. - PubMed
3. 1. Fisher RS, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) Epilepsia. 2005;46(4):470–472. - PubMed
4. 1. Helmstaedter C, et al. Chronic epilepsy and cognition: a longitudinal study in temporal lobe epilepsy. Ann Neurol. 2003;54(4):425–432. - PubMed
5. 1. Hirsch E, Schmitz B, Carreno M. Epilepsy, antiepileptic drugs (AEDs) and cognition. Acta Neurol Scand. 2003;108(s180):23–32. - PubMed